PB1996: TREATMENT PATHWAYS AT FIRST RELAPSE POST-ASCT IN MULTIPLE MYELOMA: IMPACT OF MAINTENANCE THERAPY ON TREATMENT OPTIONS
Authors: C. Duane, C. Comerford, P. Murphy, P. Thornton, J. Sargent, S. Glavey, J. Quinn
Journal: HemaSphere (2022)

Background: The introduction of new agents and treatment combinations has led to significant improvements in outcomes for multiple myeloma (MM) patients. In particular, lenalidomide maintenance therapy (LenM) following autologous stem cell transplant (ASCT) in younger/fitter MM patients has now become standard given the survival benefits associated with it. However, most MM patients will relapse post-ASCT and many effective relapse regimens have a lenalidomide backbone (e.g. KRD: carfilzomib, lenalidomide, dexamethasone, DRD: daratumumab-RD, IRD: ixazomib-RD) making choice of regimen at first relapse increasingly difficult in patients progressing during LenM therapy. Real world data reflecting these choices is needed to inform treatment decisions and consensus guidelines. Aims: We carried out an audit with an aim to: 1. Evaluate treatment and outcomes in MM patients undergoing ASCT from 2010-2020 2. Assess the impact of LenM post-ASCT and therapy choice after relapse. Methods: We carried out a retrospective audit of all patients with MM attending an Irish hospital who underwent ASCT from 2010-2020. Data was collected by chart/electronic record review. Endpoints included no. of ASCT/year and type of induction/maintenance therapy, relapse rates post-ASCT and choice of post-relapse therapy. Results: 71 patients at our centre underwent ASCT for MM between 2010-2020 (24 female,47 male) with median age of 67 and most common isotype IgG Kappa (n=33). The most frequently used induction was cyclophosphamide(C), bortezomib(V) and dexamethasone(D) (>60%, VCD). Use of maintenance therapy increased markedly over this decade, with 0% receiving maintenance in 2010, 44% in 2014 and 83% in 2020. LenM was most common, >75% (n=28).Other maintenance therapies included bortezomib n=4, daratumumab (dara)n=3 and lenalidomide + bortezomib (RV) combination n=4. First relapse treatment data was available for 36 patients. Regimens included carfilzomib/dexamethasone (KD) n=16 +/- lenalidomide (KRD) n=1, pomalidomide (PD), n=1, ixazomib (ID) n=1, dara (n=3) and dara combinations, including daraVD, n=1, and daraPD, n=1. 26 patients did not receive maintenance containing lenalidomide and the majority of these patients received ASCT pre-2015. There were n=13 relapses in this group: n=4 received lenalidomide regimens (RVD/VCD) at relapse. KD n=4, dara n=1, and ID n=1 were also used. First relapse therapy for 17 patients who progressed during LenM included: KD(n=11) 64.7%, dara(n=2) 11.7%, pomalidomide(n=1) 5.8%, and RV(n=2) 11.7% and VCD(n=1) 5.8%. Overall, carfilzomib-based therapy (without lenalidomide) was the most commonly prescribed therapy on first relapse. We observed a clear increase in its use from 2015-2020, in parallel with increased use of LenM. We also noted reducing rates of lenalidomide-based relapse therapies in later years, correlating with increased LenM. Importantly, neither DRD or PVD combinations were reimbursed for prescription in Irish healthcare during the period of audit and are notable absences from the relapse treatment regimens used. Summary/Conclusion: This audit highlights the treatment pathway and outcomes for all patients with MM undergoing ASCT over 10 years in our centre. We have noted significant changes in choice of therapy upon relapse, with carfilzomib prescription rates increasing and lenalidomide-based regimen use decreasing. Our real world data provides direct insight into the effect of widespread LenM therapy on choice of agent upon relapse and highlights the need for consensus treatment guidelines to reflect this evolution in treatment for MM patients.